Refine
Year of publication
Language
- English (62)
Has Fulltext
- yes (62)
Is part of the Bibliography
- no (62)
Keywords
- Proteomics (3)
- complexome profiling (3)
- mitochondria (3)
- Aging (2)
- Calpain (2)
- Complex I (2)
- NADPH oxidase (2)
- Podospora anserina (2)
- Reactive oxygen species (2)
- aging (2)
- bioenergetics (2)
- long non-coding RNA (2)
- mitochondrial disease (2)
- A/D transition (1)
- AAA+ disaggregase (1)
- Activities of daily living (1)
- Adult neurogenesis (1)
- Alternative oxidase (1)
- Apoptosis (1)
- Ataxia (1)
- Autoimmune vasculopathy (1)
- Autophagy (1)
- BIAM switch assay (1)
- BIAM-switch (1)
- BPTF (1)
- Behavior (1)
- Biochemistry (1)
- Brain (1)
- Calcium calmodulin kinase (1)
- Cardiac infarction (1)
- Cardiology (1)
- Cardiomyopathy (1)
- Cell signalling (1)
- Chaperone (1)
- Chemical modification (1)
- Chemiluminescence (1)
- ClpB (1)
- Complex II (1)
- Complexome profiling (1)
- Conformational change (1)
- Cortex (1)
- DNA Damage (1)
- DNA methylation (1)
- Data visualization (1)
- Database (1)
- ERAL1 (1)
- Endothelial cell (EC) (1)
- Endothelial cells (1)
- Endothelial protein C receptor (1)
- FAIR (1)
- Flavin mononucleotide (1)
- G3BP1 (1)
- HARS2 (1)
- HSP (hereditary spastic paraplegia) (1)
- Heart (1)
- Heart transplantation (1)
- Hig1 (1)
- Hypoxia inducible factor (1)
- ICAM-1 (1)
- IL-1β (1)
- Innate immunity (1)
- IntelliCage (1)
- Isoforms (1)
- KLHL11 (1)
- LARS2 (1)
- Lactic acidosis (1)
- Leukodystrophy (1)
- LncRNA - long noncoding RNA (1)
- Long non-coding RNAs (1)
- Lucigenin (1)
- Lysosome (1)
- MEIS homeodomain protein (1)
- MTRNR1 (1)
- Mass spectrometry (1)
- Membrane assays (1)
- Microparticles (1)
- Mitochondria (1)
- Mitochondrial ROS (1)
- Mitochondrial amino acid tRNA synthetases (1)
- Mitochondrial complex I (1)
- Mitochondrial disease (1)
- Mitochondrial disorder (1)
- Mitochondrial dysfunction (1)
- N-hydroxysuccinimide (1)
- N471D strumpellin knock-in mice (1)
- NADH:ubiquinone oxidoreductase (1)
- NDUFA6 (1)
- NDUFAF8 (1)
- NURF (1)
- Neonatal (1)
- Neurodegeneration (1)
- Nitric oxide (1)
- Nox (1)
- Nox4 (1)
- OXPHOS (1)
- POLG (1)
- PRLTS3 (1)
- Parkinson’s disease (1)
- Perrault syndrome (1)
- Play (1)
- Pleasure (1)
- Post-translational modifications (1)
- Posttranslational modification (1)
- Prognosis (1)
- Progranulin (1)
- Protein complex (1)
- Protein tyrosine modification (1)
- RNA Biology (1)
- RNA turnover (1)
- RNA, long noncoding (1)
- Rapamycin (1)
- Rcf1 (1)
- Redox modification (1)
- Redoxin (1)
- Release of mtDNA and mtRNA (1)
- Respiratory chain (1)
- Reverse electron transfer (1)
- SDH (1)
- SPG8 (1)
- Senescence (1)
- Starvation (1)
- Stem cell (1)
- Stroke (1)
- Stroke genetics (1)
- Subventricular zone (1)
- Superoxide (1)
- TRIM25 (1)
- TWINKLE (1)
- TWNK (1)
- Tissue-specificity (1)
- Transcription factor (1)
- Treatment (1)
- Ubiquitin (1)
- Ubiquitin ligase (1)
- Vitamin (1)
- WASH complex subunit 5 (1)
- adaptive cardiac remodelling (1)
- alternative oxidase (1)
- alternative splicing (1)
- angiogenesis (1)
- aortic aneurysm (1)
- assembly (1)
- ataxia (1)
- atherosclerosis (1)
- cGAS-STING (1)
- cancer metastases (1)
- cardiac ischaemia‐reperfusion (1)
- cardiolipin (1)
- cardiovascular disease (1)
- caspase-2 (1)
- chemotherapy resistance (1)
- colon carcinoma cells (1)
- complex I (1)
- complex I deficiency (1)
- crista junction (1)
- cristae (1)
- cytochrome c oxidase (complex IV) (1)
- data repositories (1)
- diabetes mellitus (1)
- electron transport chain (1)
- epigenomics (1)
- gene expression (1)
- glioblastoma (1)
- hypertension, pulmonary (1)
- i-AAA protease (1)
- intrinsic apoptosis (1)
- ischemia (1)
- leukodystrophy (1)
- long non-coding RNAs (1)
- macrophage (1)
- mass spectrometry (1)
- matrix metalloproteinase (1)
- membrane protein complex (1)
- membrane structure (1)
- metabolomics (1)
- molecular diagnosis (1)
- mouse (1)
- neovascularization, physiologic (1)
- nonsense-mediated mRNA decay (1)
- polyunsaturated fatty acid (1)
- proliferation (1)
- protein complexes (1)
- protein quality control (1)
- protein–protein interaction (1)
- proteomics (1)
- reactive oxygen species (1)
- remodeling (1)
- smooth muscle cell (1)
- strumpellin (1)
- temperature (1)
- therapeutics (1)
- tight junctions (1)
- vascular disease (1)
- vascular integrity (1)
- vascular remodeling (1)
- yeast (1)
Institute
Long non-coding RNAs (lncRNAs) orchestrate various biological processes and regulate the development of cardiovascular diseases. Their potential therapeutic benefit to tackle disease progression has recently been extensively explored. Our study investigates the role of lncRNA Nudix Hydrolase 6 (NUDT6) and its antisense target fibroblast growth factor 2 (FGF2) in two vascular pathologies: abdominal aortic aneurysms (AAA) and carotid artery disease. Using tissue samples from both diseases, we detected a substantial increase of NUDT6, whereas FGF2 was downregulated. Targeting Nudt6 in vivo with antisense oligonucleotides in three murine and one porcine animal model of carotid artery disease and AAA limited disease progression. Restoration of FGF2 upon Nudt6 knockdown improved vessel wall morphology and fibrous cap stability. Overexpression of NUDT6 in vitro impaired smooth muscle cell (SMC) migration, while limiting their proliferation and augmenting apoptosis. By employing RNA pulldown followed by mass spectrometry as well as RNA immunoprecipitation, we identified Cysteine and Glycine Rich Protein 1 (CSRP1) as another direct NUDT6 interaction partner, regulating cell motility and SMC differentiation. Overall, the present study identifies NUDT6 as a well-conserved antisense transcript of FGF2. NUDT6 silencing triggers SMC survival and migration and could serve as a novel RNA-based therapeutic strategy in vascular diseases.
Tight control over transcription factor activity is necessary for a sensible balance between cellular proliferation and differentiation in the embryo and during tissue homeostasis by adult stem cells, but mechanistic details have remained incomplete. The homeodomain transcription factor MEIS2 is an important regulator of neurogenesis in the ventricular–subventricular zone (V-SVZ) adult stem cell niche in mice. We here identify MEIS2 as direct target of the intracellular protease calpain-2 (composed of the catalytic subunit CAPN2 and the regulatory subunit CAPNS1). Phosphorylation at conserved serine and/or threonine residues, or dimerization with PBX1, reduced the sensitivity of MEIS2 towards cleavage by calpain-2. In the adult V-SVZ, calpain-2 activity is high in stem and progenitor cells, but rapidly declines during neuronal differentiation, which is accompanied by increased stability of MEIS2 full-length protein. In accordance with this, blocking calpain-2 activity in stem and progenitor cells, or overexpression of a cleavage-insensitive form of MEIS2, increased the production of neurons, whereas overexpression of a catalytically active CAPN2 reduced it. Collectively, our results support a key role for calpain-2 in controlling the output of adult V-SVZ neural stem and progenitor cells through cleavage of the neuronal fate determinant MEIS2.